Neuropsychological testing has revealed that affectively ill patients have impaired performance on tests involving implicit memory (priming), the Halstead Category Test, and recognition of facial emotional expression in contrast with unimpaired verbal emotion recognition tasks. The neural substrates of these deficits are systematically being explored by a variety of techniques including plans for testing patients utilizing O 15 blood flow studies with PET methodology. CAT scan studies have revealed increased VBR in patients with affective disorders unrelated to the course of illness, but positively related to age, measures of cortisol hypersecretion, and impairment on the Halstead Category Test. Our recent studies with MRI suggest decreased area of the right temporal lobe in affectively ill subjects compared with controls. Evidence of frontal hypometabolism is revealed on PET scan studies in patients with primary affective disorders as well as depression associated with epilepsy. Temporal and parietal alterations are also evident. Procaine-activation studies reveal marked alterations in psychosensory symptoms with a range of affective changes. Bipolar patients appear particularly prone to euphoric responses, while dysphoric responses occur in relationship to degree of fast activation in the EEG of temporal lobe structures. Procaine tests will be continued in patients on and off carbamazepine as well as in cocaine abusers with and without histories of panic attacks. The first studies of procaine with concurrent EEG and blood flow monitoring using O 15 PET procedures have been conducted in normal volunteers.